Here’s the dilemma
You want to set up a Multisite network with subdomains but the domain you want to use for your urls is not a WordPress site and will not be part of the network.
This doesn’t seem like an unusual case; imagine you already have our non-WordPress primary website at mainsite.com and you want your multisite blogs to live at blog1.mainsite.com and blog2.mainsite.com etc…
Typically Multisite expects there to be a blog at the domain – mainsite.com in this case – and will base new site subdomains on and the Network admin links, like http://mainsite.com/wp-admin/network/, on that url. If you create a set up your network using multisite.mainsite.com, then any new site you add will be based on that domain, so if you create site called site1 it will be given the subdomain blog1.multisite.mainsite.com, which is not what you want.
If you try to change the current site to mainsite.com in wp-config, all of your network admin links will 404 because they will point to http://mainsite.com/wp-admin/network/ which doesn’t exist, so you wont be able to create a new site at all.
The solution
The solution to this problem is actually really simple: You can change the domains of your sites after they have been set up. (d’oh! It took me a long time to realize this)
So, go ahead and set your network up using multisite.mainsite.com (this should be the current site defined in your network settings in wp-config.php). When you add a new site, it will be given a url like site1.multisite.mainsite.com; that’s fine. Once the site has been created, go to the Sites page in Network admin, where you can see the a list of all of the sites on the network; at this point you should see multisite.mainsite.com and site1.multisite.mainsite.com. Click on ‘edit’ below site1.multisite.mainsite.com and you will see a field where you can change the url. Change the domain to site1.uthsc.edu and save.
That’s it. Now, assuming your dns is configured properly, if you go to site1.mainsite.com, you will see your new WordPress site; If you go to mainsite.com, you’ll still see your primary non-WordPress site; and if you go to Network admin, you’ll see that it uses the url of the current site set in your wp-config file.
Side note: we won’t be using a wild-card for subdomains, which is probably going to be the case often in this scenario, so we’ll need to add a dns entry for each new site. In this example, multisite.mainsite.com, site1.mainsite.com, and any additional sites we add will need a dns entry to point to the IP where the network is running. If you are using a wildcard, then this doesn’t apply and all you need to do is create a new site from Network admin.