Are you maintaining your filter in another tank? If not the beneficial bacteria will die and then you'll be starting your cycle from scratch when you put it back in the betta's tank. If it's been out of the tank for more than a few days (and especially if your betta's still eating) the ammonia and nitrite are probably building up to harmful levels. Using Prime every couple of days and doing frequent large water changes will help but I would definitely buy a test kit to keep an eye on it. If he started behaving differently after you started the meds (and removed the filter) high ammonia and/or nitrite could be the reason.
For future reference if you need to use a med all you have to do is remove the carbon from the filter, not the whole filter with the biological medium in it. You can even cut open the cartridge, dump the carbon and put the cartridge back in if you want. Some meds do harm biological filters but not as much as completely removing them from use would.
Here's an interesting article on tumors in bettas:
https://www.bettacarefishguide.com/...-save-them/#Tumor_On_Your_Betta_Fish8217_Head
If it's due to a parasitic infection you could try anti-parasite meds (one that treats internal parasites). I know you mentioned you already tried Metroplex. I'm not very knowledgable about anti-parasitic meds, but I know I've heard it's more effective if you dose it via food instead of water. Otherwise, if it's not due to a parasite, I'm not sure if there's anything you could really do other than give good supportive care (high quality diet, good environment, immune supplements). If it's a benign tumor it's possible he could live for quite a while even with the tumor.