Once a lead has been sent a specific email by any campaign or program in Marketo, that's it; an engagement program will not send it to the lead a second time. It's not based off of the lead's program status or membership in a campaign, the engagement program actually checks if that specific email asset has ever been sent to the lead in the past. If so, it will skip sending that message. You would need a new lead record in order to repeat a test.
Thanks Steven. I did some testing around this and found out that it is indeed not based on Smart Campaign or program status, although if a lead is a member of a program they will be skipped. The Program will also still be skipped if removing the Smart Campaign from the Cast and replacing with a new Smart Campaign that the user hasn't been through.
What's also great is that it isn't based off of an Email within a Program, meaning you can cast anything you want such as a Webhook to an external system.