The first thing I do is hit the web to try and find the correct phone number and If I cannot I just create a pinned not in the person record that the phone number is bad. Your other options would be to delete the phone number from the record, delete, the record, or make a custom person details field that allowed you to identify if the phone number was bad. The simpler the better. deleting the phone number should allow you to sort them out with a filter anyway.
For people that are not interested I wouldn't see you doing anything aside from completing an activity with a note that identifies that they are not interested at this time.
But I don't know your business specifically and what sales cycles are like in your business.