In my case, I recently bought a 3 month old ball python. I let him settle in his new enclosure for 4 days also. It was my first ball ever so at that time, I decided to man up and handle him. He started hissing ( maybe because he was sleeping/disturbed ) so I gave him another day. The next day, I opened his enclosure. The enclosure was in good size for him (small enclo for a small snake). He started to go out of his enclosure so I handled him that time. I let him explore my hand until he gets used to it. Its been 6 months, I can safely pick him up except when he is sleeping, that's just rude! xD

Happy Keeping!